A case of CLL that was successfully treated resulted in the immediate development of AML from a coexistent myeloid line that had been suppressed

An 83 year‐old Caucasian male presented to the emergency room with confusion and lethargy. A complete blood count revealed lymphocytosis, anemia, and thrombocytopenia. A bone marrow examination revealed chronic lymphocytic leukemia (CLL), along with a small population of abnormal immature myeloid cells. Chemotherapy for CLL was started. After one cycle, repeat bone marrow examination revealed normalization of the lymphocyte count and a proliferation of the previously noted myeloid population, consistent with acute myeloid leukemia (AML). This report presents the microscopic, immunophenotypic, and cytogenetic evidence to document the development of AML after one cycle of chemotherapy for CLL.     

Gibbus deformity: Lessons from incompletely treated osteomyelitis

Gibbus deformity is defined by the collapse of one or more vertebral bodies, which results in kyphosis and is often the consequence of infection, metabolic, or congenital irregularities in the vertebrae. In this report we present a unique case of a young male with inadequately treated MRSA bacteremia complicated by lumbar osteomyelitis with progression to severe joint destruction and a marked Gibbus deformity.     

Lyme disease mimicking central nervous system lymphoma

A 33-year-old male presented with a complaint of intermittently blurred vision and right facial weakness. MRI of the brain and orbits revealed numerous cranial nerve abnormalities. There were no focal brain or spinal cord lesions. Cerebral spinal fluid flow cytometry revealed a monoclonal population of B-lymphoid cells. No other evidence of disease was found. Serum Lyme antibody was reported to be IgM positive. Therapy with ceftriaxone, was followed by improvement in his symptoms. Although flow cytometry is a useful tool in distinguishing malignancy from inflammatory disorders it does not always establish the diagnosis of malignancy by itself.     

Dual pools of actin at presynaptic terminals

We investigated actin's function in vesicle recycling and exocytosis at lamprey synapses and show that FM1-43 puncta and phalloidin-labeled filamentous actin (F-actin) structures are colocalized, yet recycling vesicles are not contained within F-actin clusters. Additionally, phalloidin also labels a plasma membrane-associated cortical actin. Injection of fluorescent G-actin revealed activity-independent dynamic actin incorporation into presynaptic synaptic vesicle clusters but not into cortical actin. Latrunculin-A, which sequesters G-actin, dispersed vesicle-associated actin structures and prevented subsequent labeled G-actin and phalloidin accumulation at presynaptic puncta, yet cortical phalloidin labeling persisted. Dispersal of presynaptic F-actin structures by latrunculin-A did not disrupt vesicle clustering or recycling or alter the amplitude or kinetics of excitatory postsynaptic currents (EPSCs). However, it slightly enhanced release during repetitive stimulation. While dispersal of presynaptic actin puncta with latrunculin-A failed to disperse synaptic vesicles or inhibit synaptic transmission, presynaptic phalloidin injection blocked exocytosis and reduced endocytosis measured by action potential-evoked FM1-43 staining. Furthermore, phalloidin stabilization of only cortical actin following pretreatment with latrunculin-A was sufficient to inhibit synaptic transmission. Conversely, treatment of axons with jasplakinolide, which induces F-actin accumulation but disrupts F-actin structures in vivo, resulted in increased synaptic transmission accompanied by a loss of phalloidin labeling of cortical actin but no loss of actin labeling within vesicle clusters. Marked synaptic deficits seen with phalloidin stabilization of cortical F-actin, in contrast to the minimal effects of disruption of a synaptic vesicle-associated F-actin, led us to conclude that two structurally and functionally distinct pools of actin exist at presynaptic sites.     

Microtomographic reconstruction of mandibular defects treated with xenografts and collagen-based membranes: A pre-clinical minipig model

Background The goal of this study was to evaluate hard tissue response following guided bone regeneration using commercially available bovine bone grafts and collagen membranes; bilayer collagen membrane and porcine pericardium-based membrane, by means of a non-destructive three-dimensional (3D) computerized volumetric analysis following microtomography reconstruction.Material and Methods Bone regenerative properties of various bovine bone graft materials were evaluated in the Göttingen minipig model. Two standardized intraosseous defects (15mm x 8mm x 8mm) were created bilaterally of the mandible of eighteen animals (n=72 defects). Groups were nested within the same subject and randomly distributed among the sites: (i) negative control (no graft and membrane), (ii) bovine bone graft/bilayer collagen membrane (BOB) (iii) Bio-Oss® bone graft/porcine pericardium-based membrane (BOJ) and (iv) cerabone® bone graft/porcine pericardium-based membrane (CJ). Samples were harvested at 4, 8, and 12-week time points (n=6 animal/time point). Segments were scanned using computerized microtomography (μCT) and three dimensionally reconstructed utilizing volumetric reconstruction software. Statistical analyses were performed using IBM SPSS with a significance level of 5%.Results From a temporal perspective, tridimensional evaluation revealed gradual bone ingrowth with the presence of particulate bone grafts bridging the defect walls, and mandibular architecture preservation over time. Volumetric analysis demonstrated no significant difference between all groups at 4 weeks (p>0.127). At 8 and 12 weeks there was a higher percentage of new bone formation for control and CJ groups when compared to BOB and BOJ groups (p<0.039). The natural bovine bone graft group showed more potential for graft resorption over time relative to bovine bone graft, significantly different between 4 and 8 weeks (p<0.003).Conclusions Volumetric analysis yielded a favorable mandible shape with respect to time through the beneficial balance between graft resorption/bone regenerative capacity for the natural bovine bone graft. Key words:3D reconstruction, microCT, grafting material, pre-clinical model.     

Safety and efficacy of total dose infusion of 1,020 mg of ferumoxytol administered over 15 min

For the majority of patients with iron deficiency anemia (IDA), a full course of intravenous (IV) iron is 1 g. Most IV irons require 5–10 administrations of 100–300 mg. We have successfully employed 1 g low molecular weight iron dextran over 1 hr. For further convenience for patients and physicians, we explored the administration of 1.02 g of ferumoxytol over 15 min instead of the approved 2 × 510 mg injections. Sixty patients with IDA, (hemoglobin <11 g/dL, transferrin saturation [TSAT] ≤20%, and ferritin <100 ng/mL) with an inadequate response or intolerance to oral iron, received 1020 mg ferumoxytol over 15 min. Vital signs were measured for 1 hr. Adverse events (AEs) were collected via telephone at 1, 2, and 7 days. Follow‐up visits occurred at 4 and 8 weeks for efficacy assessments. The primary endpoint was safety and tolerability. Secondary efficacy endpoints included mean change in hemoglobin, TSAT, and red cell distribution width. No serious adverse events (SAEs) occurred. Fifty‐eight patients received the planned dose. Twenty‐six out of sixty (43.3%) patients reported AEs of which 13 were mild and transient during infusion. All resolved within minutes. Fourteen patients reported self‐limited arthralgias, myalgias, and/or headache within 24–48 hr. At Baseline, the mean hemoglobin was 9.4 g/dL. The mean increments at Week 4 and 8 were 2.1 and 2.6 g/dL, respectively. Ferumoxytol, administered as 1.02 g infusion over 15 min was well tolerated with no SAEs and demonstrated excellent efficacy. If corroborated in future studies this represents an improved method of treating IDA. Am. J. Heamtol. 88:944–947, 2013. © 2013 Wiley Periodicals, Inc.